Shahryar Ahmad

Clostridium difficile infection in hospitalized liver transplant patients: A nationwide analysis

The incidence of Clostridium difficile infection (CDI) is increasing among hospitalized patients. Liver transplantation (LT) patients are at higher risk for acquiring CDI. Small, single‐center studies (but no nationwide analyses) have assessed this association. We used the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project (2004‐2008) for this retrospective, cross‐sectional study. Patients with any discharge diagnosis of LT composed the study population, and they were identified with International Classification of Diseases, Ninth Revision, Clinical Modification codes. Those with a discharge diagnosis of CDI were considered cases. Our primary outcomes were the prevalence of CDI and the effects of CDI on inpatient mortality. Our secondary outcomes included the length of stay and hospitalization charges. A regression analysis was used to derive odds ratios (ORs) adjusted for potential confounders. There were 193,174 discharges with a diagnosis of LT from 2004 to 2008. The prevalence of CDI was 2.7% in the LT population and 0.9% in the non‐LT population (P < 0.001). Most of the LT patients were 50 to 64 years old. LT patients had higher odds of developing CDI [OR = 2.88, 95% confidence interval (CI) = 2.68‐3.10]. Increasing age and increasing comorbidity (including inflammatory bowel disease and nasogastric tube placement) were also independent CDI risk factors. CDI was associated with a higher mortality rate: 5.5% for LT patients with CDI versus 3.2% for LT‐only patients (adjusted OR = 1.70, 95% CI = 1.29‐2.25). In conclusion, the prevalence of CDI is higher for LT patients versus non‐LT patients (2.7% versus 0.9%). CDI is an independent risk factor for mortality in the LT population. Liver Transpl, 2012.

Chronic Kidney Disease and End-Stage Renal Disease Predict Higher Risk of Mortality in Patients with Primary Upper Gastrointestinal Bleeding

Background: The outcome of gastrointestinal bleeding in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients is difficult to discern from the literature. Many publications are small, single-center series or are from an era prior to advanced interventional endoscopy, widespread use of proton pump inhibitors or treatment for Helicobacter pylori infections. In this study, we quantify the role of CKD and ESRD as independent predictors of mortality in patients admitted to the hospital with a principal diagnosis of primary upper gastrointestinal bleeding (UGIB). Methods: We used the Nationwide Inpatient Sample that contains data on approximately 8 million admissions in 1,000 hospitals chosen to approximate a 20% stratified sample of all US facilities. Patients discharged with the principal diagnosis of primary UGIB, CKD or ESRD were identified through the ninth revision of the International Classification of Diseases, clinical modification (ICD-9-CM) codes. The outcome variables included frequency and in-hospital mortality of UGIB in CKD and ESRD patients as compared to non-CKD patients and were analyzed using logistic regression modeling. Results: In 2007, out of a total of 398,213 admissions with a diagnosis of primary UGIB, 35,985 were in CKD, 14,983 in ESRD, and 347,245 in non-renal disease groups. The OR for primary UGIB hospitalization in CKD and ESRD was 1.30 (95% CI 1.17–1.46) and 1.84 (95% CI 1.61–2.09), respectively. The corresponding all-cause mortality OR was 1.47 (95% CI 1.21–1.78) and 3.02 (95% CI 2.23–4.1), respectively. Conclusion: Patients with CKD or ESRD admitted with primary UGIB have up to three times higher risk of all-cause in-hospital mortality, warranting heightened vigilance by their clinicians.

Severe sepsis in hematopoietic stem cell transplant recipients

Objective:Severe sepsis requires timely management and has high mortality if care is delayed. Hematopoietic stem cell transplant recipients are more likely to be immunocompromised and are predisposed to serious infections. Reports of outcomes of severe sepsis in this population are limited to data from single, tertiary care centers, and national outcomes data are missing. Design:Retrospective analysis of an administrative database. Setting:Twenty percent of community hospitals in United States, excluding federal hospitals. Subject:Patients with severe sepsis. Intervention:None. Measurements and Main Results:We used International Classification of Diseases, 9th Edition, Clinical Modification codes indicating the presence of sepsis and organ system failure to identify hospitalizations for severe sepsis between 2000 and 2008. We also used International Classification of Diseases, 9th Edition, Clinical Modification codes to identify hematopoietic stem cell transplant recipients. We compared outcomes of hematopoietic stem cell transplant recipients with severe sepsis during engraftment and subsequent admissions with a non–hematopoietic stem cell transplant cohort and excluded solid-organ transplantation from this cohort. We used mixed effect, multivariate logistic regression modeling with propensity score adjustment to examine factors associated with mortality of severe sepsis in hematopoietic stem cell transplant recipients. A total of 21,898 hematopoietic stem cell transplant recipients with severe sepsis were identified. The frequency of severe sepsis in hematopoietic stem cell transplant recipients was five times higher when compared with the non–hematopoietic stem cell transplant cohort. The unadjusted mortality was 32.9% in non–hematopoietic stem cell transplant cohort, which was similar to autologous hematopoietic stem cell transplant recipients (30.1%) and those who did not develop graft-versus-host disease (35%). Mortality was significantly higher in allogeneic transplants (55.1%, p < 0.001) and in those who developed graft-versus-host disease (47.9%, p < 0.001). After adjustment, during engraftment admission, the odds of in-hospital mortality in allogeneic hematopoietic stem cell transplant (odds ratio, 3.81; 95% CI, 2.39–6.07) and autologous hematopoietic stem cell transplant (odds ratio, 1.28; 95% CI, 1.06–1.53) recipients was significantly higher than non–hematopoietic stem cell transplant patients. Similarly, in subsequent admissions, hematopoietic stem cell transplant recipients with graft-versus-host disease (odds ratio, 2.14; 95% CI, 1.88–2.45) and without graft-versus-host disease (odds ratio, 1.35; 95% CI, 1.19–1.54) had significantly higher odds of mortality than non–hematopoietic stem cell transplant patients. Among patients with hematopoietic stem cell transplant, persons with autologous hematopoietic stem cell transplant and those without graft-versus-host disease fared better as compared with their allogeneic and graft-versus-host disease counterparts. Conclusions:Hematopoietic stem cell transplant recipients are more likely to develop severe sepsis and die following a severe sepsis episode than nontransplant patients. Autologous hematopoietic stem cell transplant recipients and those who do not develop graft-versus-host disease have significantly better outcomes than allogeneic and graft-versus-host disease patients.

Infections in Liver Disease

Infectious complications are common occurrences in end-stage liver disease (ESLD). Frequent infections precipitate decompensation of liver disease leading to acute or chronic liver failure, organ dysfunction, de-listing from transplant, and major morbidity and mortality. The spectrum of microorganisms has shifted with the emergence of multidrug-resistant strains, which has major implications for both therapy and prophylaxis. Cirrhosis is often associated with an underlying noninfectious systemic inflammatory state that makes diagnosis of infections particularly challenging. Adequate resuscitation and timely administration of appropriate antibiotics are pivotal to improved outcomes from infections in ESLD.

Effect of a Rapid Response Team on Patient Outcomes in a Community-Based Teaching Hospital

BACKGROUND Rapid response teams have been adopted across hospitals to reduce the rate of inpatient cardiopulmonary arrest. Yet, data are not uniform on their effectiveness across university and community settings. OBJECTIVE The objective of our study was to determine the impact of rapid response teams on patient outcomes in a community teaching hospital with 24/7 resident coverage. METHODS Our retrospective chart review of preintervention-postintervention data included all patients admitted between January 2004 and April 2006. Rapid response teams were initiated in March 2005. The outcomes of interest were inpatient mortality, unexpected transfer to the intensive care unit, code blue (cardiac or pulmonary arrest) per 1000 discharges, and length of stay in the intensive care unit. RESULTS Rapid response teams were activated 213 times during the intervention period. There was no statistically significant difference in inpatient mortality (3.13% preintervention versus 2.91% postintervention), code blue calls (3.09 versus 2.89 per 1000 discharges), or unexpected transfers of patients to the intensive care unit (15.8% versus 15.5%). CONCLUSIONS The implementation of a rapid response team did not appear to affect overall mortality and code blue calls in a community-based hospital with 24/7 resident coverage.

National trends in lung volume reduction surgery in the United States: 2000 to 2010.

Lung volume reduction surgery (LVRS) is used to treat advanced emphysema that is refractory to maximal medical therapy. 1 Th e National Emphysema Treatment Trials (NETT) have shown their effi cacy in improving 6-min walk distance, maximal exercise capacity, and quality of life, although the mortality benefi t may be limited to the upper-lobe predominance, low-baseline exercise group. 2 , 3 We, therefore, examined the newer trends in LVRS from 2000 to 2010 to see if LVRS is still popular in United States.

Immunonutrition in Acute Respiratory Distress Syndrome

Purpose of ReviewDietary supplementation with nutrients such as glutamine and omega-3 fatty acids to modulate/boost host immunity in critical illness is a new concept. We review current evidence (animal and human studies) on the role of immunonutrition in acute respiratory distress syndrome (ARDS).Recent FindingsDietary supplementation during stress states (ARDS) with omega-3 fatty acids has been shown to attenuate inflammation and improve lung microvascular permeability in animals. In humans, omega-3 fatty acid supplementation has shown mixed results. While studies show improvement in oxygenation and lung mechanics, a recent study demonstrated increased mortality with omega-3 fatty acids. Similarly, animal studies suggest that lower glutamine levels are associated with worse outcomes in surgical and septic patients. But, a recent study in humans has shown an increased trend towards all-cause mortality.SummaryCurrent evidence is conflicting and does not support use of immune-modulating therapies (glutamine or omega-3 fatty acids) in ARDS.

Su1694 Outcomes of Cardiothoracic Surgery in Cirrhosis

Background: L-carnitine (4-N-trimethyl ammonium 3-hydroxybutyric acid) is a naturally occurring amino acid that functions to transfer long-chain fatty acids across the mitochondrial membrane, enabling oxidative release of energy. The primary sources of l-carnitine are endogenous synthesis by the liver and kidney and dietary intake. It has been shown that cirrhotic patients become gradually l-carnitine deficient because of poor synthesis and reduction in dietary intake. An administration of l-carnitine is an accepted treatment for mitochondrial myopathy and encephalomyopathy, as well as other states of primary and secondary l-carnitine deficiency. In this study, we examined the effect of l-carnitine on muscle cramping and peripheral blood cell abnormality in patients with liver cirrhosis. Methods: A total of 23 cirrhotic patients at Osaka Medical College from December 2011 to October 2012 were enrolled in this study (13 male, mean age 69±9 Y/O, mean Child Pugh score 7.2±1.2). All patients have diagnosed as liver cirrhosis by laboratory data, imaging test or liver biopsy. Patients were administrated a 300mg of l-carnitine tablet twice a day. The evaluation of muscles cramp was investigated by using an original questionnaire and serum creatine kinase (CK) level. Also, peripheral blood cells profile and other liver function parameters were examined 1, 3, 6 months after treatment. Results: Muscle crump was significantly improved in the majority (90%) of patients 1 month after treatment (p , 0.01). Serum CK levels were also significantly decreased after l-carnitine administration (186±121 vs. 106±70 mg/dl, p , 0.05). Blood platelet count was significantly increased 3 months after treatment (10.0±4.5 vs. 11.7±4.0 x104 /dl, p , 0.01). Moreover, serum ammonia levels were significantly decreased 1 month after treatment (136 ±92 μg/dl vs. 64±32 μg/ dl, p, 0.01). Prothrombin time was significantly increased 3 months after treatment (79±14 vs. 84±18, p, 0.05). Serum albumin, bilirubin level and Child-Pugh score were not different after treatment. No serious adverse events have been occurred in this study. Discussion: Currently, l-carnitine supplementation in dialysis patients has been used for the treatment of muscle cramping. On the other hands, l-carnitine has been proposed as a potential adjuvant treatment to improve anemia, thrombocytopenia, leukopenia and immunological function. Thrombocytopenia occurs up to 70% of patients with liver cirrhosis and increases the risk of bleeding. Frequent muscle crump is worsen a QOL of cirrhotic patients. The lcarnitine supplement may offer the possibility of improving the QOL and prognosis in patients with liver cirrhosis.

Sa1028 Iatrogenic Infections in Hospitalized Cirrhotics Predict Mortality

Background/Aims:Muscle cramps are common in patients with cirrhosis, particularly when diuretics are used for ascites. Its pathophysiologic mechanism remains uncertain. In this work, we conducted field testing of a questionnaire to measure the extent and severity of muscle cramps in patients with cirrhosis and explored plasma metabolomic biomarkers for muscle cramps. Methods: Patients with an established diagnosis of cirrhosis were prospectively contacted prior to their follow-up appointment in our liver clinic. Patients were asked to fill out a muscle cramps questionnaire (mMCQ) which asks about occurrence, frequency, location and impact (sleep and daily living) of muscle cramps. Blood samples were drawn after a minimum of 12 hours of fasting, which were promptly cold-centrifuged and plasma was separated for metabolomics assays. Results: In this on-going study, 109 patients have been contacted to date, of whom 46 patients have responded to the questionnaire (response rate=42% to date). The respondents were 57.8 ± 11.1 years of age and 59% were men. The mean MELD score was 12.8 ± 5.5. Approximately half (46%) reported history of hepatic encephalopathy and 6.5% refractory ascites requiring therapeutic paracentesis. In this patient cohort, the prevalence of muscle cramps was 76%. Of those who reported muscle cramps, 50% had moderate to severe symptoms (occuring at least daily or causing at least moderate disturbance of activities of daily living). To date, we have assayed 25 amino acid in the plasma samples (n=43), including taurine, threonine, serine, asparagine, glutamic acid, argininosuccinic acid, glutamine, proline, glycine, alanine, citruline, α-amino-N-butyric acid, valine, cysteine, methionine, isoleucine, leucine, tyrosine, phenyl alanine, β-alanine, ornithine, lysine, histidine, arginine, and allo-isoleucine. Of these, plasma cysteine levels were significantly different according to the severity of muscle cramps. In patients without muscle cramps the median plasma level was 59 nmol/mL with an interquartile range (IQR) of 52-75 nmol/mL, compared to those with cramps (median=82 nmol/mL, IQR=61-94). In the figure, patients with severe cramps had the highest cysteine levels (median 90 nmol/ mL, IQR=78-106) compared to those with mild cramps (median:73 nmol/mL, IQR=51-86). Conclusion: Muscle cramps are extremely common in patients with cirrhosis receiving ongoing care at a liver clinic. Plasma cysteine levels may be a potential biomarker for muscle cramps, as they correlate with their occurrence and severity.

Sa1029 Acute Kidney Injury (AKI) Predicts Mortality in Hospitalized Patient With Cirrhosis

Background/Aims:Muscle cramps are common in patients with cirrhosis, particularly when diuretics are used for ascites. Its pathophysiologic mechanism remains uncertain. In this work, we conducted field testing of a questionnaire to measure the extent and severity of muscle cramps in patients with cirrhosis and explored plasma metabolomic biomarkers for muscle cramps. Methods: Patients with an established diagnosis of cirrhosis were prospectively contacted prior to their follow-up appointment in our liver clinic. Patients were asked to fill out a muscle cramps questionnaire (mMCQ) which asks about occurrence, frequency, location and impact (sleep and daily living) of muscle cramps. Blood samples were drawn after a minimum of 12 hours of fasting, which were promptly cold-centrifuged and plasma was separated for metabolomics assays. Results: In this on-going study, 109 patients have been contacted to date, of whom 46 patients have responded to the questionnaire (response rate=42% to date). The respondents were 57.8 ± 11.1 years of age and 59% were men. The mean MELD score was 12.8 ± 5.5. Approximately half (46%) reported history of hepatic encephalopathy and 6.5% refractory ascites requiring therapeutic paracentesis. In this patient cohort, the prevalence of muscle cramps was 76%. Of those who reported muscle cramps, 50% had moderate to severe symptoms (occuring at least daily or causing at least moderate disturbance of activities of daily living). To date, we have assayed 25 amino acid in the plasma samples (n=43), including taurine, threonine, serine, asparagine, glutamic acid, argininosuccinic acid, glutamine, proline, glycine, alanine, citruline, α-amino-N-butyric acid, valine, cysteine, methionine, isoleucine, leucine, tyrosine, phenyl alanine, β-alanine, ornithine, lysine, histidine, arginine, and allo-isoleucine. Of these, plasma cysteine levels were significantly different according to the severity of muscle cramps. In patients without muscle cramps the median plasma level was 59 nmol/mL with an interquartile range (IQR) of 52-75 nmol/mL, compared to those with cramps (median=82 nmol/mL, IQR=61-94). In the figure, patients with severe cramps had the highest cysteine levels (median 90 nmol/ mL, IQR=78-106) compared to those with mild cramps (median:73 nmol/mL, IQR=51-86). Conclusion: Muscle cramps are extremely common in patients with cirrhosis receiving ongoing care at a liver clinic. Plasma cysteine levels may be a potential biomarker for muscle cramps, as they correlate with their occurrence and severity.